In combinatorial chemistry, a large number of compounds, substances or chemicals are created from a relatively small set of precursors. Subsequently these compounds are evaluated for suitability for a particular application. Compared to traditional discovery methods, combinatorial methods sharply reduce the costs associated with preparing and screening each compound.
This new research technology allows rapid screening of large sets of compounds or mixtures of compounds. As a result the discovery of new drugs, catalysts and materials is accelerated. The associated decrease in development time and costs has revolutionized the discovery of new drugs, catalysts and materials.
The development of compounds suitable for a particular application can be subdivided into two main steps. The first step is compound synthesis. The second step is the screening of these compounds for a specific reaction or property. Either of these steps can be time consuming thereby limiting the speed of improvement.
Because of the large number of candidate materials, parallel screening and synthesis of compounds is used. Often suitable compounds have to be added to other substances under specific conditions. Common conditions are temperatures and pressures, using reactive gases, other than ambient. Two kinds of devices are commonly used for screening and synthesis of compounds under varying conditions.
One is the glass bomb, which consists of a thick walled glass container. Such a bomb contains one compound and a stir bar for magnetically stirring the contents of the bomb. The bomb is closed with an elastic rubber gasket and crown or crimp-cap. Pressures above ambient can be maintained in such a container. This is achieved by using a pressure supplying needle that penetrates the gasket. Additional compounds can be added in liquid form, while the bomb is pressurized, using a needle and syringe combination.
Several disadvantages are apparent using such an apparatus. Because of the use of breakable glass the apparatus is potentially unsafe. This is especially so when used with spontaneous combustible precursors and flammable gases or solvents. The pressure range over which this apparatus can be used is limited. This is due to the strength of the crimp-cap/gasket combination. The range of compounds that can be synthesized or tested is limited by the leaching of substances present in the gasket. These substances can poison the screened compounds or contaminate the synthesized compounds. This in turn limits the lowest testable concentration of the screened compounds. This can be a disadvantage when compounds are difficult or expensive to make. Furthermore solids cannot be added directly to the content of the bomb in a simple way. Compounds that are added using the syringe and needle combination cannot easily be saturated with gas. The use of compounds not saturated with gas can modify screening conditions in an unpredictable way. Furthermore the syringe has to be compatible with the compound added and the reaction conditions used. Lubricants and materials used in manufacturing syringes for instance can poison screened compounds. When glass bombs are used for parallel screening and synthesis, the number of reactions that simultaneous and reproducibly can be run can be limited by the injection time of additional compounds. Furthermore the accumulation of the previously mentioned disadvantages hinders parallel processing.
The other is the metal reactor. The reactor consists of a usually thick walled metal container closed with a metal lid. The lid often incorporates a mechanical stirrer. In addition often one or more tubes, including valves, as well as sensors are connected to the reactor. The tubes are used to introduce compounds into the reactor or remove compounds from the reactor. Both processes can take place at pressures and temperatures other than ambient. In parallel screening and synthesis of compounds, syringes are commonly used to introduce compounds into the reactor in combination with the mentioned valves and tubes.
However, the incorporation of several valves and tubes makes the manufacturing of such a apparatus expensive. Especially when metal reactors are used for parallel processing expensive modifications are necessary. Like the glass bomb, solids cannot be added directly to the content of the reactor. Compounds that are added using a syringe cannot easily be saturated with gas. The syringe used has to be compatible with the reaction conditions and the added compound. When metal reactors are used for parallel screening and synthesis, the number of reactions that simultaneous and reproducibly can be processed can be limited by the injection time of additional compounds. Furthermore the accumulation of the previously mentioned disadvantages hinders parallel processing.